Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
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Abstract
Objective
To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients.
Methods
Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects.
Results
In total, 21% ( n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% ( n = 6). Non-survivors had higher serum concentrations of NfL ( p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses ( p = 2.6 × 10 –7 ) and unadjusted analyses ( p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors ( p = 0.02).
Conclusion
Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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SciScore for 10.1101/2020.09.07.20189415: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Ethical considerations: Informed consents were obtained from all patients or next-of-kin if patients were incapacitated of giving consent. Randomization not detected. Blinding Measurement of GFAp and NfL in serum samples were performed in the Clinical Neurochemistry Laboratory at the Sahlgrenska University Hospital, Sweden, by board-certified laboratory technicians blind to clinical data. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Using a modified version of the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC)/World Health Organization (WHO) … SciScore for 10.1101/2020.09.07.20189415: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Ethical considerations: Informed consents were obtained from all patients or next-of-kin if patients were incapacitated of giving consent. Randomization not detected. Blinding Measurement of GFAp and NfL in serum samples were performed in the Clinical Neurochemistry Laboratory at the Sahlgrenska University Hospital, Sweden, by board-certified laboratory technicians blind to clinical data. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Using a modified version of the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC)/World Health Organization (WHO) Clinical Characterization Protocol (CCP), clinical and routine data were abstracted from electronic medical records and deposited into an ISARIC (http://isaric.tghn.org) REDCap database (Research Electronic Data Capture, Vanderbilt University, TN, hosted by University of Oxford, UK). REDCapsuggested: (REDCap, RRID:SCR_003445)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:In this pilot study there are several limitations. First, the number of patients with full data sets available was modest. Secondly, detailed and systematic neurological, neurophysiological and neuroradiological investigations were not possible to perform, since our patients were treated under medical isolation procedures at different units and several patients needed ventilatory support in ICUs. Thus, possible association between GFAp and NfL and specific CNS manifestations may have been undetected in this study. In order to study further the questions raised by our observations, we plan a follow-up study of COVID-19 patients up to a year after diagnosis including a systematic neurological assessment. In conclusion, elevated concentrations of NfL and GFAp in COVID-19 patients seem to be potential prognostic markers in COVID-19. Further studies will be essential in order to elucidate the pathogenesis and the clinical importance of the COVID-19 disease affecting the nervous system and how this can be measured and treated. Prospective neurological and cognitive assessment of individuals with COVID-19 will also be crucial to understand the natural history of COVID-19 in the CNS and monitor for any long-term neurological sequelae.31
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04381819 Recruiting Norwegian SARS-CoV-2 Study - Virological, Clinical and Immun… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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